A Study of Ad26.COV2.S in Adults (COVID-19)

Inclusion criteria:

• Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose, procedures, and potential risks and benefits of the study, and is willing to participate in the study
• All female participants of childbearing potential must have a negative highly sensitive urine pregnancy test at screening; and have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration
• Participant must have a body mass index (BMI) less than or equal to (<=) 30.0 kilograms per square meter (kg/m^2)
• Applicable to Cohorts 1 and 2 only: Participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, clinical laboratory assessments, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe coronavirus disease-2019 (COVID-19). Applicable to Cohort 3 only: In the investigator's clinical judgment, participant must be either in good or stable health Participants may have underlying illnesses such as hyperlipoproteinemia or hypothyroidism, as long as their symptoms and signs are medically controlled and not considered to be comorbidities related to an increased risk of severe COVID-19 (participants may have medical conditions of mild severity (according to the Toxicity Grading Scale), including hypertension or high blood pressure, as long as their symptoms and signs are stable and medically controlled as defined by no change in medication over the past 6 months [except for issues of tolerability or use of similar drug with same mechanism of action, for example, thiazides, Beta blockers, Alpha blockers at the same effective dose]). If they are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of physical examination, clinical laboratory assessments medical history, and vital signs (participants can be enrolled with Grade 1 or Grade 2 values for vital signs measurements)
• Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine

Exclusion criteria:

• Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0 degree Celsius within 24 hours prior to the planned first dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor
• Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
• Participant has a history of any neurological disorders or seizures including Guillain-Barre syndrome, with the exception of febrile seizures during childhood
• Participant has a positive diagnostic test result for SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) at screening
• Participants with comorbidities that are or might be associated with an increased risk of progression to severe COVID-19, that is, participants with moderate-to-severe asthma; chronic lung diseases such as chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), idiopathic pulmonary fibrosis and cystic fibrosis; diabetes (including type 1, type 2, or gestational); serious heart conditions, including heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and (pulmonary) hypertension or high blood pressure; obesity (BMI >= 30 kg/m^2); chronic kidney disease being treated with dialysis; participants who are immunocompromised (as outlined in other exclusion criteria); chronic liver disease, including cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic conditions (dementia); smoking; and participants who live in nursing homes or long-term care facilities. Investigators must refer to the complete list of conditions that increase the risk of progression to severe COVID-19 available at the Centers for Disease Control and Prevention (CDC) website. Applicable to Cohort 3 only: Participants may have medical conditions of mild severity (according to the Toxicity Grading Scale), including hypertension or high blood pressure, as long as their symptoms and signs are stable and medically controlled in the judgment of the investigator
• Applicable to Cohorts 1 and 3 only: Participant currently working in an occupation with a high risk of exposure to SARS-CoV-2 (for example, health care worker or emergency response personnel) or considered at the investigator's discretion to be at increased risk to acquire COVID-19 for any other reason